What does an abnormal alpha-fetoprotein (AFP) level indicate?

Abnormal Alpha-Fetoprotein (AFP) Levels: Clinical Indications and Significance

Abnormal alpha-fetoprotein (AFP) levels can indicate several serious conditions including hepatocellular carcinoma, neural tube defects in fetuses, certain genetic disorders, and other malignancies, with the specific clinical significance depending on patient context and the degree of elevation.

Maternal Serum AFP Elevations

Abnormal maternal serum AFP (MSAFP) levels during pregnancy can indicate:

• Open neural tube defects (ONTDs): Elevated levels (typically >2.0 MoM) are associated with anencephaly or open spina bifida cystica 1

• Other adverse pregnancy outcomes:

  • Imminent miscarriages
  • Fetal demise
  • Eventual prematurity
  • Open ventral wall defects 1

• Low MSAFP levels: May indicate increased risk for Down syndrome 1

Important considerations for MSAFP interpretation:

• Results must be interpreted with accurate gestational age determination 2
• Optimal testing window is between 15-20 weeks gestation 1
• False positives and negatives can occur; this is a screening test, not diagnostic 1
• Demographic factors (race, maternal diabetes, maternal weight) influence MSAFP distribution 2

Elevated AFP in Adults and Children

Elevated AFP levels outside pregnancy can indicate:

• Hepatocellular carcinoma (HCC):

  • AFP >200 ng/mL is highly suggestive of HCC in at-risk individuals 1
  • Used in combination with ultrasound for HCC surveillance in high-risk groups 1
  • Normal in up to 35% of small HCC cases, limiting sensitivity 1

• Other malignancies:

  • Undifferentiated tumors of testis and ovary 3
  • Teratomas and tumors of primitive gut origin 4
  • Certain childhood cancers 5

• Genetic disorders:

  • Ataxia-telangiectasia (AT): Increased serum AFP levels are virtually pathognomonic for AT in the appropriate clinical context (seen in 95% of patients) 1
  • Other chromosomal repair disorders 1

• Liver disease:

  • Acute and chronic hepatitis (typically temporary elevations) 3, 4
  • Active hepatocyte regeneration 1

Clinical Applications of AFP Testing

HCC Surveillance

• Recommended for high-risk groups including:

  • Asian male hepatitis B carriers over age 40
  • Asian female hepatitis B carriers over age 50
  • Hepatitis B carriers with family history of HCC
  • Cirrhotic hepatitis B carriers
  • Individuals with hepatitis C cirrhosis
  • Individuals with genetic hemochromatosis and cirrhosis 1

• Surveillance protocol:

  • Ultrasound with or without AFP every 6 months 1
  • AFP cutoff of ≥200 ng/mL is diagnostic for HCC in lesions ≥2 cm 1

Genetic Disorder Screening

• AFP screening is essential for suspected AT patients 1
• Monitoring AFP trends is important in tyrosinemia type I 2

Limitations and Pitfalls

• Limited sensitivity: AFP is normal in up to 35% of small HCC cases 1
• Nonspecific elevations: Can occur with active hepatitis or hepatocyte regeneration 1
• Age-dependent interpretation: AFP levels are normally high in neonates and decline throughout the first year of life 5
• Trend importance: For conditions like HCC, the trend of AFP values over time is often more important than a single measurement 2

Key Points for Clinical Practice

• AFP interpretation must always consider patient context (pregnancy status, age, liver disease risk factors)
• Serial measurements are often more valuable than single readings
• AFP should be used in combination with imaging for HCC surveillance
• In pregnancy, MSAFP is a screening test requiring follow-up diagnostic procedures for abnormal results
• Extremely high AFP levels in adults strongly suggest malignancy, particularly HCC